Therapeutic expression of human clotting factors IX and X following adeno-associated viral vector-mediated intrauterine gene transfer in early-gestation fetal macaques.

ABSTRACT: Adeno-associated viral vectors (AAVs) achieve stable therapeutic expression without long-term toxicity in adults with hemophilia. To avert irreversible complications in congenital disorders producing early pathogenesis, safety and efficacy of AAV-intrauterine gene transfer (IUGT) requires assessment. We therefore performed IUGT of AAV5 or -8 with liver-specific promoter-1 encoding either human coagulation factors IX (hFIX) or X (hFX) into Macaca fascicularis fetuses at ∼0.4 gestation. The initial cohort received 1 × 10¹² vector genomes (vgs) of AAV5-hFIX ( n = 5; 0.45 × 10¹³ vg/kg birth weight), resulting in ∼3.0% hFIX at birth and 0.6-6.8% over 19-51 mo. The next cohort received 0.2-1 × 10¹³ vg boluses. AAV5-hFX animals ( n = 3; 3.57 × 10¹³ vg/k

SUBMITTER: Chan JKY 

PROVIDER: S-EPMC6404563 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature